Caloric restriction (CR) extends lifespan and reduces various age-related changes. The aim of the present study was to investigate whether CR can correct existing manifestations of cardiac aging in senescent animals independent from its beneficial effects on the progression of arteriosclerosis.

Methods: 

Left ventricular (LV) samples were obtained from male young-adult and senescent Sprague-Dawley rats before and after 6 months of caloric restriction (-40%) or control-diet. LV function, mitochondrial respiratory function, LV fibrosis and the expression of apoptotic markers were measured.

Results: 

The myocardium of senescent rats (22–24 months at the beginning of the study) was characterized by reduced LV systolic (fractional shortening, ejection fraction) and diastolic function (E/A ratio) as well as mitochondrial dysfunction. The expression of proapoptotic genes (Bcl-xS, Bax) or apoptotic activation was extremely low in young animals but higher in old animals. CR in senescent rats (24+6 months) reduced mortality, retarded the age-associated deterioration of LV function and reduced the overload indicators BNP/ANP compared to age-matched rats on control diet. Similarly, disturbances in mitochondrial function and apoptotic activation were reduced compared to senescent rats on control diet. However, diastolic function was modified mainly in young animals (6+6 months) by CR. Accordingly, serum parameters indicating increased collagen deposition leading to fibrosis (TIMP-1, MMP-1) and collagen content in LV tissue sections were reduced in young animals but remained high in old animals after CR.

Conclusion: 

Basic mechanisms for cardioprotective effects of caloric restriction are preserved in the senescent heart. Their activation results in an improvement of survival and LV function, although they are insufficient to modify cardiac fibrosis in old animals. The impact and protective mechanisms of CR on LV function appear to be different in young and senescent animals. Modification of cardiometabolic pathways may represent a novel and useful therapeutic strategy to preserve LV function in aged myocardium.